Reduction of Brain Calcium After Consumption of Diets Deficient in Calcium or Vitamin D

Abstract: Rats fed diets deficient in calcium or vitamin D for 4 weeks displayed hypocalcemia, as indicated by a 50% reduction in serum calcium and a sevenfold elevation of serum parathyroid hormone. These treatments also decreased the calcium content of brain tissue. On a regional basis. this effect was greatest in the brain stem (24% decrease) and least in striatum (10% decrease). Subcellular analysis indicated that the depletion of brain calcium was greatest in the soluble and the microsomal fractions. Infusion of calcium solutions reversed the depletion of brain calcium produced by dietary deficiencies. In control rats. parathyroidectomy or infusion of parathyroid hormone did not alter the calcium content of brain tissue, although these treatments affected the levels of calcium in the serum. In general, these treatments had no effect on the magnesium content of serum or brain tissue. However, vitamin D deficiency did increase the magnesium content of the myelin and synaptosomal fractions. This increase was reversed by parathyroidectomy. These observations demonstrate that long-term hypocalcemia produces distinct changes in the localization of calcium and magnesium in brain tissue. Furthermore. these studies suggest that though brain calcium levels are influenced by serum concentrations, serum changes must be of large magnitude and long duration for brain calcium levels to be affected.     

Endocrine Control of Calcium Metabolism in Teleosts

It is evident that fishes regulate their serum calcium efficientlybut that endocrine systems involved may be different from thosein tetrapods. A functional parathyroid gland has not yet beendemonstrated in fishes. The majority of evidence indicates thatcalcitonin has little or no effect on fish calcium regulation.Instead, the corpuscles of Stannius and the pituitary glandare necessary for maintaining fish serum calcium levels. Inthe killifish, Fundulus heteroclitus, the removal of the corpusclesproduces hypercalcemia in sea water but not in artificial seawater deficient in calcium. Transplants of the corpuscles orthe administration of corpuscle homogenate corrects the increasein calcium. On the other hand, hypophysectomy elicits hypocalcemiaunder calcium deficient conditions but not in calcium rich seawater. Replacement therapy with pituitary homogenate or hypophysialtransplant prevents the fall in calcium. It is postulated thatthe hypocalcemic corpuscles of Stannius and the hypercalcemicpituitary gland enable the euryhaline killifish to regulateits serum calcium levels in high calcium sea water and low calciumfresh water, respectively.     

1,25-Dihydroxyvitamin D and not calcium is the major regulator of calbindin-D 9-kDa mRNA levels in vivo.

A possible role of calcium in vivo on intestinal calbindin-D 9-kDa mRNA levels has been studied in rats. In vitamin D-deficient rats, a marked increase in dietary calcium has a small but significant effect on calbindin-D 9-kDa mRNA levels, despite a dramatic increase in serum calcium concentration that clearly resulted from increased intestinal absorption of calcium. On the other hand, vitamin D under all circumstances increased calbindin-D 9-kDa mRNA levels, with the greatest levels found in animals on a low calcium diet where little or no calcium is available for absorption. These results strongly support the idea that 1,25-dihydroxyvitamin D is directly responsible for the induction of calbindin-D 9-kDa.     

High calcium intake does not prevent stress-salt hypertension in dogs

Avoidance conditioning sessions and isotonic saline (1.3 L/day) were administered to dogs for 12 days under conditions of a low (0.1%) or high (1.5%) calcium diet. Twenty-four-hour mean arterial pressure increased comparably during the stress-salt conditioning periods on both the low (systolic: +16 +/- 5 mm Hg; diastolic: +6 +/- 2 mm Hg) and high (systolic: +17 +/- 4 mm Hg; diastolic: +11 +/- 4 mm Hg) calcium diets. Urine volume, sodium excretion, and serum calcium levels on the high calcium diet were not significantly different from those on the low calcium diet. In a second experiment, calcium was infused continuously for six days into the arterial circulation of normotensive or stress-salt hypertensive dogs at a rate of 0.12-0.23 mEq/min. Although serum calcium levels increased by up to 50% under these conditions, there were no significant effects on 24-hour levels of arterial pressure. In contrast to the protective effect of augmented potassium intake, these findings indicate that calcium intake does not influence the development of stress-salt hypertension in dogs.     

Role of prolactin in human milk composition and serum lipids studied during suppression of galactorrhea with bromocriptine

Bromocriptine suppressed lactation by depressing the serum prolactin (PRL) level in 10 of 12 cases with profuse galactorrhea. The PRL level in galactorrhea milk was lower than in serum and was similar to that obtained in normal mature milk. However, significantly higher total solid, total ash, lipid and calcium levels, and reduced lactose and potassium levels were seen in galactorrhea specimens compared to mature milk. Although all the constituents decreased during treatment, the highly significant reduction in lipid and calcium levels shows the predominant effect of PRL on mammary synthesis and/or transport of these constituents. Fasting serum total lipids, total cholesterol and triglyceride levels were significantly higher in the galactorrhea group than in breast-feeding women with established lactation, suggesting that elevated serum PRL plays a role in lipid metabolism.     

Norepinephrine Induced Hypocalcemia in Sheep

Increased plasma levels of non-esterified fatty acids (NEFA) may lead to several physiological changes e.g. increased insulin secretion with a concomitant reduction of blood glucose, decreased glucose utilization in heart and skeletal musculature and increased blood acetone levels. High NEFA levels also cause fat infiltration in various organs especially the liver. Recently Akgün & Rudman (1969) showed that ACTH induced NEFA mobilization in rabbits was followed by hypocalcemia. Serum calcium decreased about 30 %, while the calcium content in adipose tissue increased up to 1000 %. This finding could also be verified in vitro. When adipose tissue was incubated in serum containing lipolytic hormones, lipolysis was stimulated and there was a shift of calcium from serum to tissue. A negative correlation between serum calcium and NEFA in hypocalcemic cows was reported earlier (Luthman & Jonson 1969). The purpose of the present investigation was to study the effect of increased NEFA levels on serum calcium in sheep. The animals used were ewes in late pregnancy. Lipolysis was stimulated by norepinephrine (Norexadrin, Astra). The animals were given a continuous intravenous infusion during 8 hrs. at a rate of 1 μg/kg/min. The methods of analysis were the same as described before (Luthman & Jonson).     

Estrogen receptor genes polymorphisms determine serum lipid profile in healthy postmenopausal women treated with calcium,vitamin D,and genistein

Cardiovascular risk increases in women after menopause. Unfavorable lipid-lipoprotein changes due to a lack of estrogens may have an important role in this context. Estrogen actions are mainly mediated by their binding to two estrogen receptors (ERs) whose signaling may be conditioned by different factors. Calcium, vitamin D, and genistein, among others, cause a beneficial effect on serum lipid profile by its modulation. Some genetic factors can also determine this signal. We determined the possible additive effect of genistein on calcium and vitamin D supplementation regarding serum lipid profile changes and whether ER polymorphisms may mediate in this effect. We performed a prospective, double blind study in which women were randomized in two groups: one group received calcium and vitamin D and the other group received calcium, vitamin D and genistein. Subsequently, we studied rs9340799, rs928554, and rs4986938 ER polymorphisms in both groups. Our results showed that being a carrier of the variant allele G of rs928554 polymorphism was associated with a greater decrease in triglyceride levels and that the homozygous AA genotype of rs9340799 polymorphism was associated with a greater decrease in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels after calcium, vitamin D, and genistein supplementation. This is the first report showing an association between polymorphisms in ER genes and an improvement of the serum lipid profile after taking calcium, vitamin D, and genistein supplementation in postmenopausal women. It reinforces the hypothesis that genetic factors are crucial in ER signalling.     

低钙透析液联合醋酸钙对血液透析患者高磷血症的影响

目的：研究低钙透析液联合醋酸钙治疗对血液透析患者血磷、血钙及甲状旁腺激素iPTH水平的影响。方法：将30例维持性血液透析患者随机分为试验组和对照组,在试验期间所有患者均低磷饮食,两组透析液钙浓度均为1．25mmol／L,试验组同时给予醋酸钙治疗,对照组不应用醋酸钙治疗,三个月后观察和比较两组患者的血钙、血磷及血iPTH水平的变化。结果：治疗前,两组各组血磷、血钙、血磷和血iPTH的水平比较差异均无统计学意义（P〉0．05）。治疗后,对照组血钙水平明显下降（P〈0．05）,血iPTH水平略上升但无统计学意义（P〉0．05）,血磷水平无显著变化（P〉0．05）;试验组血iPTH水平略下降（P〉0．05）,血钙水平无明显变化（P〉0．05）,但血磷明显下降（P〈0．05）;且试验组血磷水平较对照组明显下降（P〈0．05）,血钙水平显著高于对照组（P〈O．05）,但在正常范围内,两组血iPTH水平比较无统计学意义（P〉0．05）。结论：低钙透析液联合醋酸钙治疗可有效降低血液透析患者的血磷水平,且不会导致高钙血症的发生。     

Effect of parathyroid hormone on the increase in serum glucose and insulin levels after a glucose load to thyroparathyroidectomized rats.

Thyroparathyroidectomy (TPTX) caused a significant increase in serum glucose and a corresponding fall in serum calcium in both fed and fasted rats. The increase in serum glucose, induced by TPTX, was markedly potentiated by a single intraperitoneal administration of calcium (2 mg/100 g BW) which caused a significant elevation of serum calcium in thyroparathyroidectomized rats. Parathyroid hormone (PTH; 20 U/100 g BW) administered subcutaneously to thyroparathyroidectomized rats, caused a significant decrease in serum glucose (0.1 g/100 g BW) to sham-operated rats significantly increased both serum glucose and insulin. The rise of serum glucose produced by a glucose load was markedly potentiated by TPTX, but the increase in serum insulin was not promoted significantly. The administration of PTH decreased both serum glucose and insulin levels increased by a glucose load to thyroparathyroidectomized rats, in a dose-dependent manner. The administration of calcitonin (80 MRC mU/100 g BW) significantly prevented the effect of PTH to decrease serum glucose after a glucose load to thyroparathyroidectomized rats, and calcitonin increased serum insulin. These results suggest that the effect of PTH on serum glucose does not involve insulin secretion.     

Serum calcium concentrations in white sucker, Catostomus commersoni Lacepède, and bluegill, Lepomis macrochirus Rafinesque, in northern Wisconsin lakes: relation to pH and waterborne calcium

We measured serum calcium concentrations in mature white suckers and bluegills collected from clear-water Wisconsin lakes before spawning. The mean serum calcium concentration in female white suckers was greater in a circumneutral lake than in two naturally acidic lakes, whereas mean concentrations in fish from the two acidic lakes did not differ. Serum calcium concentrations in female bluegills from four acidic and four circumneutral lakes varied among lakes, but no relation was apparent between serum calcium level and either lake pH or waterborne calcium. In contrast, a strong negative correlation between mean serum calcium concentration and relative density of bluegill populations in the eight lakes was observed, suggesting that serum calcium levels in this species are affected by density-dependent factors. Mean serum calcium concentrations were substantially lower in mature male bluegills than in females, which is the norm prior to spawning. We hypothesized that serum calcium levels in female white suckers are depressed by exposure to pH 6.0 or less in calcium-poor waters. The utility of serum calcium concentrations, measured before spawning, as a measure of pH-related stress on populations of white suckers and other synchronous spawners merits further study. However, this measure is probably not useful for evaluating acid stress on fish species such as the bluegill, which have asynchronous reproductive cycles.     

Calcium behavior in endotoxin-poisoned mice: especially calcium accumulation in mitochondria

A possible role of intracellular Ca2+ and participation of calmodulin in cellular metabolism in endotoxin-poisoned mice were investigated. The levels of calcium in liver cytosol and liver mitochondria fractions in poisoned mice were markedly higher 18-48 hr after endotoxin injection than in the control mice. On the other hand, the levels of serum calcium in the poisoned mice were about 20% lower at 18 hr than in the controls. The serum calcium levels in mice injected with 50 and 100 micrograms of endotoxin showed no dose-response effect, but a dose-response effect was observed at a dose of 200-400 micrograms. The serum Ca2+ levels in endotoxin-tolerant mice were similar to those in the control mice. The levels in mice injected with glucocorticoid-antagonizing factor mice were about 14% lower at 3 hr than in the controls. The mice fed a vitamin D3- and calcium-free diet showed a higher mortality rate in the early stage (12-18 hr) of endotoxication than that of the mice fed a normal diet. The lipid peroxide levels and Ca2+-ATPase activity in the liver mitochondria fraction in endotoxin-poisoned mice showed a higher level than those of the control mice. There was little or no difference in the levels of serum glucose between the mice injected with calmodulin antagonist (trifluoperazine, TFP) plus endotoxin and those given endotoxin alone. However, the liver glycogen levels in TFP plus endotoxin-treated mice were markedly higher than that in mice given endotoxin alone. Furthermore, calcium antagonist (verapamil) plus endotoxin-treated mice had about a 40% higher survival rate after 72 hr than those given endotoxin alone. The findings suggest that there is a possibility of participation of the Ca2+-calmodulin system in carbohydrate metabolic disorders during endotoxemia and that the changes in intracellular Ca2+ may result in various metabolic disorders.     

Effect of lithium on hepatic and serum elemental status under different dietary protein regimens

Lithium carbonate at the dose level of 1.1 g/kg was administered in diet to normal (18% protein), low-protein-(LP; 8%) and highprotein (HP; 30% diet)-fed rats for a period of 1 mo. The LP diet resulted in a significant decrease in the hepatic levels of zinc, iron, copper, manganese, calcium, and serum levels of calcium and sodium. The HP diet caused a marked decrease in copper and calcium levels in liver, but an increase in potassium levels in serum was observed. Lithium treatment to normal rats led to a significant reduction in the hepatic contents of zinc, copper, potassium, calcium, and serum contents of potassium and sodium, whereas an elevation in serum contents of calcium was noticed. Administration of lithium to protein-deficient rats increased the hepatic concentration of manganese and serum concentration of calcium and the levels almost reached the normal limits. On the other hand, there was a marked depression in potassium contents in the serum of LP-as well as HP-fed rats following lithium treatment when compared to LP and HP groups, respectively.     

The effects of fasting and refeeding on serum parathormone and calcitonin concentrations in young and old male rats.

Although fasting and refeeding reveal the existence of age-related changes in carbohydrate and lipid metabolism, the effects of aging on mineral metabolism in refed animals are unknown. We therefore investigated hormonal regulation of calcium metabolism in young (4 months) and old (26 months) male rats fasted for 48 hours and then refed for 4 or 24 hours. Serum concentrations of total and ionized calcium and parathormone were similar in control young and old rats. Serum calcitonin level was higher, and the concentrations of albumin and inorganic phosphate and alkaline phosphatase activity were lower in fed old rats. In young fasted rats, the serum ionized and total calcium was decreased, and phosphate concentration was increased. In old rats, fasting resulted in the increase of serum parathormone level. Fasting reduced serum alkaline phosphatase activity to a similar extent in both age groups. In young rats, refeeding for 24h normalized serum calcium and phosphate levels and alkaline phosphatase activity, and decreased serum concentrations of PTH and calcitonin. In old refed rats, serum calcitonin concentration was raised by 77% compared to fed or fasted animals, whereas parathormone levels were normalized. Our results indicate that old fasted or refed rats maintain normal serum calcium concentration in a different way than young animals, possibly through the increase in serum levels of parathormone and/or calcitonin. Thus, dietary manipulations such as fasting and refeeding constitute an interesting model for the investigation of the effects of aging on the hormonal regulation of serum calcium level.     

Effect of Ca level on 65Zn absorption at the ligated duodenal loop of rat

Effect of calcium concentration on Zn absorption was studied in rats. Administration of Zn solution with calcium through gastric tracts depressed markedly the levels of Zn in serum taken from portal vein. Dependency on calcium concentrations of the absorption and distribution of Ca in the body was determined using in situ administration of Zn into ligated duodenal loop of rats. Administration of Zn with high calcium solution decreased significantly the levels of Zn in serum and all the tissues compared with the administration with low and medium calcium solutions. A considerable disease in the level of Zn was observed in the liver and kidney compared with the rats administered with medium and low calcium solutions.     

Serum osteocalcin levels do not change during rapidly induced hypercalcemia in healthy subjects.

Since osteocalcin has been suggested to play a role in calcium homeostasis, we investigated its serum levels in 6 healthy subjects during a rapid calcium infusion. Serum levels of intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25-(OH) D3] and 1,25-dihydroxyvitamin D [1,25-(OH)2 D3] were also determined. The calcium infusion increased plasma-ionized calcium levels from 1.25 +/- 0.04 to 1.54 +/- 0.07 mmol/l at 30 min (p less than 0.05). Concomitantly, serum levels of intact PTH declined from 2.1 +/- 0.9 to 0.2 +/- 0.3 mmol/l (p less than 0.05). In contrast, serum osteocalcin levels did not change. Further, during calcium infusion, serum levels of 1,25-(OH)2 D3 decreased from 81 +/- 17 to 75 +/- 15 pmol/l (p less than 0.05) whereas serum levels of 25-(OH) D3 did not change. The results therefore suggest that calcium per se does not influence osteocalcin secretion.     

Peripheral effects of PTH are not altered after thyroid surgery in euthyroid patients

BACKGROUND: We have previously found decreased serum levels of both ionized calcium and 1,25(OH)2D and an increase in serum phosphate levels at 1 year after hemithyroidectomy. However, basal and stimulated parathyroid hormone (PTH) secretions were not altered. To investigate whether the observed biochemical changes after unilateral thyroid surgery may be due to a relative end-organ resistance to PTH, we studied the peripheral effects of infused hPTH-(1-34) in 6 patients preoperatively and 3 months after hemithyroidectomy. METHODS: Serum levels of TSH, FT4 and FT3 were measured pre- and postoperatively. hPTH-(1-34) was infused at 0.9 IU/kg/h during 6 h. Blood samples for analysis of ionized calcium, intact PTH, phosphate, 25(OH)D, 1,25(OH)2D and urinary samples for calcium, phosphate and nephrogenous(n)-cAMP analysis were taken at baseline, when the infusion was discontinued after 6 h and at 24 h. RESULTS: Three months after hemithyroidectomy, serum levels of FT3 were decreased and TSH levels increased. Pre- and postoperative hPTH-(1-34) infusions induced increased serum levels of ionized calcium, 1,25(OH)2D, increased urinary excretion of phosphate and elevated n-cAMP levels. The changes in the studied biochemical variables during the hPTH-(1-34) infusions did not differ between the two study occasions. CONCLUSION: By using a 6-hour hPTH-(1-34) infusion protocol, we have shown that the peripheral PTH effect is not altered by a slight reduction in thyroid hormone levels at 3 months after hemithyroidectomy.     

Effects of oral supplementation with stable strontium

The biologic effects of stable strontium, a naturally occurring trace element in the diet and the body, have been little investigated. This paper discusses the effects of oral supplementation with stable strontium in laboratory studies and clinical investigations. The extent of intestinal absorption of various doses of orally administered strontium was estimated by determining serum and tissue levels with atomic absorption spectrophotometry. The central observation is that increased oral intake produces a direct increase in serum levels and intracellular uptake of strontium. The results of these studies, as well as those of other investigators, demonstrate that a moderate dosage of stable strontium does not adversely affect the level of calcium either in the serum or in soft tissues. In studies of patients receiving 1 to 1.5 g/d of strontium gluconate, a sustained increase in the serum level of strontium produced a 100-fold increase in the strontium:calcium ratio. In rats, studies indicate that an increase in intracellular strontium content following supplementation may exert a protective effect on mitochondrial structure, probably by means of a stabilizing effect of strontium on membranes. The strontium:calcium ratio in animals receiving a standard diet is higher in the cell than in the extracellular fluid; this may be of physiologic significance.An increase in density that corresponded to the deposition of stable strontium was observed in areas of bone lesions due to metastatic cancer in patients receiving stable strontium supplementation. This suggests the possibility of using strontium to mineralize osteophenic areas and to relieve bone pain. Also, because of reports of an inverse relation between the incidence of dental caries and a high strontium content in drinking water, the use of natural water containing relatively high levels of stable strontium should be considered. In each of these instances it is important to maintain a normal dietary intake of calcium.     

Decreased thiamine and magnesium levels in the potentiation of the neurotoxicity of lead in occupational lead exposure

The relationship between blood lead (Pb) and serum levels of calcium and of neural nutrients such as thiamine and magnesium (Mg) has been determined in a Nigerian population that is occupationally exposed to Pb. Forty-seven male Pb workers were recruited as test subjects and 25 males unexposed to Pb served as controls. The test subjects were classified into three groups, based on severity of exposure to Pb. Blood lead (BPb) and the serum levels of Mg, thiamine, and calcium were determined in both test subjects and controls. The mean blood Pb level was not significantly higher in Pb workers. In contrast, Mg and thiamine levels were significantly decreased (p<0.05; p<0.01, respectively). However, the calcium level was not significantly lower in test subjects than in controls. Also, there was a significant negative correlation between serum thiamine and blood Pb levels (r=-0.50; p<0.01). Furthermore, there was a significant negative correlation between serum calcium and BPb levels (r=-0.41; p<0.01). This study has shown that relatively low BPb levels can enhance Pb absorption and also potentiate Pb neurotoxicity in the presence of decreased serum thiamine and Mg levels.     

睾酮对去睾丸家兔骨密度及血清钙磷的影响

目的:观察去睾丸和睾酮补充对雄兔骨密度和血清钙、镁、磷的影响.方法:周龄相同的雄性新西兰白兔随机分成对照组、去睾丸组和睾酮补充组(去睾丸后肌注十一酸睾酮).同等条件下饲养20周后测量各组兔全身骨密度、腰椎骨密度、股骨颈骨密度,并检测血清总睾酮(TT)、雌二醇(E2),脱氢表雄酮(DHEA)水平以及血清钙(Ca2 )、游离钙([Ca2 ]i)镁(Mg2 )、磷(P)和碱性磷酸酶(AKP)浓度.结果:去睾丸组血清TT水平明显下降(P<0.01),睾酮补充组血清TT水平升高接近对照组(P>0.05).去睾丸组血清E2和E2/TT比明显高于对照组(P<0.01),睾酮补充组血清E2和E2/TT下降,接近对照组水平(P均>0.05).与对照组相比,去睾丸组血清Ca2 、[Ca2 ]i、Mg2 以及AKP浓度明显升高(P均<0.01),睾酮补充组血清Ca2 、[Ca2 ]i、Mg2 以及AKP浓度较去睾丸组低,接近对照组水平(P>0.05).股骨颈骨密度在去睾丸组明显低于对照组和睾酮补充组(P<0.01),而后两组无差别(P>0.05).结论:去睾丸后雄兔血清TT明显下降,E2和E2/TT比以及Ca2 、[Ca2 ]i、Mg2 和AKP浓度明显升高,骨密度显著下降,睾酮补充使上述异常明显改善.     

氯沙坦对慢性肾功能不全患者血红蛋白、电解质及NO水平的影响

目的:探讨氯沙坦对慢性肾脏功能不全患者血红蛋白、电解质及NO水平的影响。方法:收集我院收治的慢性肾功能不全患者140例,根据用药不同分为对照组和实验组,每组各70例,对照组给予洛汀新口服治疗,实验组给予氯沙坦口服治疗。分别于治疗前后检测两组患者血红蛋白(Hb)、红细胞压积(HCT)、血钙、血磷、血钾、内皮素(ET)及一氧化氮(NO)的水平。结果:与治疗前比较,两组患者治疗后Hb、HCT、血钙及NO水平升高,而血钾、血磷及ET水平降低,差异具有统计学意义(P0.05);与对照组比较,实验组患者治疗后Hb、HCT、血钙及NO水平较高,而血钾、血磷及ET水平较低,差异具有统计学意义(P0.05)。结论:氯沙坦能够明显升高慢性肾功能不全患者血红蛋白及NO水平,恢复电解质平衡,改善预后,对临床具有指导意义。